Venous smooth muscle contractility, extensibility, and apparent synthesis of prostaglandins are enhanced in spontaneously hypertensive rats. These changes are not secondary to the hypertension since veins are not exposed to the increased intravascular pressure of the hypertension. Therefore, venous smooth muscle provides a model for the study of intrinsic defects in vascular smooth muscle function in experimental hypertension, uncomplicated by the effects of an increased intravascular pressure. This application for a research grant outlines a series of studies designed to evaluate the role alterations in vascular smooth muscle function play in the pathogenesis of the increased arterial resistance of renal hypertension. The hypothesis to be tested is that alterations in vascular smooth muscle function precede the development of the increased resistance of renal hypertension. Prevention of these changes in function will prevent the development of hypertension. Utilizing the two-kidney Goldblatt hypertensive dog, we will measure 1) arterial and venous smooth muscle responses to vasoactive agents before and during the development of the hypertension employing the perfused Mesentary bed and gracilis muscle 2) the effect of prophylactic anti-hypertensive therapy on vascular smooth muscle function and development of high blood pressure during induction of hypertension and 3) the relationship between the changes in vascular function and development of the hypertension. The parameters to be measured include 1) responses of the perfused preparations to vasoactive agents and nerve stimulation 2) vascular compliance and 3) electron-microscopic ultrastructure of the arterial and venous smooth muscle. With these data it will be possible to define the role, if any, the vascular smooth muscle may contribute to the pathogenesis versus the maintenance of the hypertensive state. Once this hypothesis has been tested and the results evaluated, experiments will be initiated to evaluate the potential mechanisms of vascular dysfunction in hypertension.